What can be added to Abilify (aripiprazole) to address mood instability, increased depression, and anxiety in a patient with first psychosis schizophrenia?

Augmentation Strategy for Aripiprazole in First-Episode Psychosis with Mood Instability

For a patient with first-episode schizophrenia on Abilify 10 mg experiencing increased depression, anxiety, and possible negative symptoms, add an SSRI for anxiety and depressive symptoms while ensuring the aripiprazole dose is optimized and extrapyramidal symptoms are ruled out. 1

Initial Assessment Before Adding Adjunctive Treatment

Before adding any medication, you must determine whether symptoms represent:

• Extrapyramidal side-effects (EPS) masquerading as negative symptoms or depression - Aripiprazole can cause akathisia, bradykinesia, or parkinsonism that may appear as anxiety, agitation, or apathy 1, 2
• Core depressive symptoms concurrent with psychosis - In first-episode patients, 75% have depressive symptoms at baseline, with 98% resolving as psychosis remits 3
• Post-psychotic depression - Occurs after acute symptoms stabilize and requires different management 4

Primary Recommendation: SSRI Augmentation

Add an SSRI (such as sertraline, escitalopram, or fluoxetine) for anxiety and depressive symptoms after confirming adequate antipsychotic dosing for 4-6 weeks. 1

Rationale and Evidence:

• The American Academy of Child and Adolescent Psychiatry recommends adjunctive SSRI therapy specifically for anxiety management in mixed presentation schizophrenia 1
• SSRIs are effective for post-psychotic depression in patients on maintenance antipsychotics 4
• This approach addresses both anxiety and depressive symptoms without increasing dopaminergic activity

Critical Caveat - Rule Out EPS First:

• If bradykinesia or parkinsonism is present, reduce aripiprazole dose or switch to quetiapine/olanzapine rather than adding medications 1
• Aripiprazole's partial dopamine agonism can paradoxically worsen agitation and anxiety in some patients, particularly those previously on full dopamine antagonists 5
• The Lancet Psychiatry prioritizes dose reduction or switching over adding antiparkinsonian agents when EPS are suspected 1

Alternative Considerations Based on Symptom Profile

If Predominantly Negative Symptoms:

Consider low-dose aripiprazole augmentation (increasing current dose modestly) or switching to cariprazine, which has specific efficacy for negative symptoms. 6

• New atypical antipsychotics like cariprazine and lurasidone show effectiveness against negative and cognitive symptoms 6
• However, ensure 4-6 weeks at therapeutic aripiprazole levels before concluding inadequate response 1

If Treatment-Resistant Features:

Consider clozapine if the patient has failed two adequate trials of antipsychotics (including the current aripiprazole trial). 7, 1

• The APA recommends clozapine for treatment-resistant schizophrenia with 1B evidence 7
• Clozapine may be superior to conventional antipsychotics in patients with psychotic mood disorder or schizoaffective features 4
• The Lancet Psychiatry suggests clozapine consideration after two failed adequate trials 1

Essential Non-Pharmacological Adjuncts

Simultaneously initiate cognitive-behavioral therapy for psychosis (CBTp) and psychoeducation for patient and family. 7, 1

• CBTp has 1B evidence for modest but lasting positive effects on cognition and symptoms 1
• Psychoeducation has strong evidence (1B rating) for improving functioning and reducing relapse rates 1
• The APA recommends both interventions as core treatments, not optional add-ons 7

Monitoring and Timeline

Acute Phase (First 6-18 Months):

• Depression concurrent with active psychosis typically resolves as psychosis remits - avoid premature antidepressant addition 3
• Monitor for depressive symptoms that persist beyond psychotic symptom resolution, which warrant SSRI treatment 3
• Depressive symptoms were prodromal to relapse in only 7% of first-episode patients 3

Critical Period (Up to 5 Years):

• Maintain intensive biopsychosocial care continuously - depression, suicide risk, and social anxiety should be actively identified and treated 7
• Side-effects like weight gain, sexual dysfunction, and sedation can retard recovery and must be monitored regularly 7
• Continuity of care with the same treating clinician for at least 18 months is essential 7

Common Pitfalls to Avoid

1. Adding antidepressants during acute psychosis - In actively psychotic patients, neuroleptic plus antidepressant may be less effective than neuroleptic alone 4

2. Misinterpreting EPS as negative symptoms - Aripiprazole-induced akathisia or parkinsonism can mimic anxiety, depression, or negative symptoms 1, 5

3. Premature polypharmacy - Ensure 4-6 weeks at adequate aripiprazole doses before adding adjuncts 1

4. Ignoring psychosocial interventions - These are not optional; they have equivalent evidence strength to pharmacotherapy 7, 1

5. Overlooking substance use - This strongly predicts medication non-adherence and complicates treatment 7